Cyclooxygenase-2: A possible target in schistosoma-associated bladder cancer

Objective: To analyse and compare the expression of cyclooxygenase (COX) enzymes in schistosoma-associated bladder cancer, and to determine any association with tumour grade or stage. Materials and methods: Sixty paired samples of tumour and adjacent nonmalignant urothelium were identified. There were 25 squamous and 28 transitional cell carcinomas, and seven adenocarcinomas. Serial sections were obtained and a standard three-layer immunohistochemistry protocol, using COX-1- and COX-2-specific mouse monoclonal antibodies, applied. Results: COX-1 was expressed mostly in nonvascular smooth muscle with weak reactivity in malignant and nonmalignant urothelium. Nonmalignant urothelium expressed COX-2 weakly, notably in areas of dysplasia and squamous metaplasia whereas there was a significant increase in COX-2 (P<0.001) with moderate to strong granular cytoplasmic expression in all three malignant histological types. The COX-2 reactivity was higher in transitional and adenocarcinomas than in squamous cell carcinoma (P<0.001). Areas of carcinoma in situ showed COX-2 reactivity comparable with that in invasive areas and more intense than that detected in dysplastic or metaplastic urothelium (P<0.001). There was a statistically significant positive correlation between COX-2 expression and tumour grade (P=0.0052). Conclusion: COX-2 is over-expressed in schistosoma-associated bladder cancer, consistent with a potential role for COX-2 inhibitors in the prevention and management of this disease.